factor A

General Information (Source: NCBI Gene,UniProt)

Text mining Term	factor A
UniProt ID	GSK3B_RAT
Name	Glycogen synthase kinase-3 beta Serine/threonine-protein kinase GSK3B Factor A FA GSK-3 beta
Gene Names	Gsk3b
Taxonomy	Rattus norvegicus

General annotation

Function	Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta- cells. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity.
Subcellular location	Cytoplasm (By similarity). Nucleus (By similarity). Membrane. Cell membrane (By similarity). Note=The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosophorylated form to the cell membrane (By similarity).

Function

Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta- cells. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity.

Subcellular location

Cytoplasm (By similarity). Nucleus (By similarity). Membrane. Cell membrane (By similarity). Note=The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosophorylated form to the cell membrane (By similarity).

Gene Ontology

GO:0043407	negative regulation of MAP kinase activity	BP
GO:0005977	glycogen metabolic process	BP
GO:0048168	regulation of neuronal synaptic plasticity	BP
GO:0030877	beta-catenin destruction complex	CC
GO:0030010	establishment of cell polarity	BP
GO:0043197	dendritic spine	CC
GO:0045892	negative regulation of transcription, DNA-dependent	BP
GO:0005829	cytosol	CC
GO:0019901	protein kinase binding	MF
GO:0035255	ionotropic glutamate receptor binding	MF
GO:0042493	response to drug	BP
GO:0051534	negative regulation of NFAT protein import into nucleus	BP
GO:0050321	tau-protein kinase activity	MF
GO:0009968	negative regulation of signal transduction	BP
GO:0032886	regulation of microtubule-based process	BP
GO:0005524	ATP binding	MF
GO:0010226	response to lithium ion	BP
GO:0050774	negative regulation of dendrite morphogenesis	BP
GO:0004674	protein serine/threonine kinase activity	MF
GO:0006917	induction of apoptosis	BP
GO:0005625	soluble fraction	CC
GO:0005178	integrin binding	MF
GO:0034747	Axin-APC-beta-catenin-GSK3B complex	CC
GO:0001837	epithelial to mesenchymal transition	BP
GO:0048156	tau protein binding	MF
GO:0005886	plasma membrane	CC
GO:0045121	membrane raft	CC

Sequence

>gi|14091770|ref|NP_114469.1| glycogen synthase kinase-3 beta [Rattus norvegicus]
MSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTKVIGNGSFGVV
YQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDEVYLNLVLDYVPETVY
RVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRG
EPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQ
IREMNPNYTEFKFPQIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKL
PNGRDTPALFNFTTQELSSNPPLATILIPPHARIQAAASPPANATAASDTNAGDRGQTNNAASASASNST

Database Cross Reference

Ensembl Gene	ENSRNOT00000003867
UniGene	Rn.10426
PDB
RefSeq	NP_114469.1
Pfam	PF00069

PTID

factor A

General Information (Source: NCBI Gene,UniProt)

General annotation

Gene Ontology

Sequence

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Database Cross Reference